Engram Reactivation and Depression - Annissa DeSilva


In Ramirez et al. 2015, the optogenetic reactivation of a positive memory engram in the dentate gyrus (DG) was sufficient to increase struggling behavior in the tail suspension test (TST), increase the consumption of sucrose in the sucrose preference test (SPT), and decreased latency in the novelty suppressed feeding test (NSFT). What I found most interesting about this paper was that the acute reactivation of the DG engram only relived symptoms temporarily, however chronic reactivation of the neurons over 5 days showed reversal of stress induced symptoms. Additionally, histological analysis revealed that mice under all stressed conditions, except for the 5-day chronic activation group and control had decreased neurogenesis, in fact the 5-day chronic and the control group actually had increased neurogenesis. I think that the researchers included this data point to assert that this positive memory activation could serve as a potential treatment method for depression, especially emphasizing the fact that neurogenesis was seen after 5 days versus 2 weeks as observed in anti-depressant treatment. As discussed previously, neurogenesis in the hippocampus may not be the cause of the anti-depressant efficacy however anti-depressant action may promote brain-derived neurotrophic factor (BDNF), a neurotropic factor that stimulates neurogenesis and may provide a therapeutic effect through long term potentiation (LTP). This is relevant to the current study because BDNF is implicated in the formation of context learning and memory. Studies have found increased BDNF levels in hippocampi of mice after learning tasks such as the Morris water maze (Kesslak, So, Choi, Cotman, & Gomez-Pinilla, 1998). BDNF is also theorized to be an essential factor for synaptic plasticity related to long term memory storage (Lee, 2004). The authors suggest that their research opens the possibility of further research relating the two, perhaps the activation of the positive engram stimulates BDNF transcription or is up-regulated in some way to potentially contribute to the alleviation of depressive symptoms seen with anti-depressants. It has been theorized that those with depression display decreased positive memory learning potentially due to lack of LTP in the hippocampus (Dillon, 2015) which could contribute to anhedonia. In the future it would be interesting to compare the effectiveness of chronic DG engram reactivation and chronic anti-depressant use in multiple behavioral assays to truly evaluate this method use as a potential treatment and its specific effect.
The pairing of the two papers were very interesting regarding future clinical treatment of depression. After reading both papers, it seemed as if the natural progression of the research was to investigate if positive false memories can be made, and if so, can we alter a true negative memory with the false positive memory leading to a reversal of stress induced depressive behavior? The idea of changing the emotionality of a memory is reminiscent of cognitive behavioral therapy (CBT) where the aim is to alter negative thoughts into positive ones however, the researchers suggest that this engram activation is more salient than external positive stimuli, if true the effect of engram activation may result in a more “efficient” therapy.


Citations:

Dillon, D. G. (2015). The neuroscience of positive memory deficits in depression. Frontiers in Psychology,6. doi:10.3389/fpsyg.2015.01295
Kesslak, J. P., So, V., Choi, J., Cotman, C. W., & Gomez-Pinilla, F. (1998). Learning upregulates brain-derived neurotrophic factor messenger ribonucleic acid: A mechanism to facilitate encoding and circuit maintenance? Behavioral Neuroscience,112(4), 1012-1019. doi:10.1037/0735-7044.112.4.1012
Lee, J. L. (2004). Independent Cellular Processes for Hippocampal Memory Consolidation and Reconsolidation. Science,304(5672), 839-843. doi:10.1126/science.1095760

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